Diminished ovarian reserve generally reflects the processes of follicular depletion and decline in oocyte quality, and a female with diminished ovarian reserve has a greatly reduced chance of conceiving.
It is known that the level of follicle stimulating hormone (FSH) in blood measured at day 3 of the menstrual cycle is a good predictor of ovarian reserve. Whilst serum tests are the “gold standard”, they are not suited to home use and, for convenience, urine tests would be preferable.
Urinary tests for FSH are commercially available (e.g. the Serono Maiaclone FSH test, Amersham Amerlex FSH test), but these tests have several disadvantages.
The Serono and Amersham tests both require the collection of timed urine samples (typically two samples passed 3 hours apart) and must be calibrated to take account of the total sample volume in order to give a result in terms of quantity of FSH per hour. The need to measure urine volume (equivalent to dilution) and the uncertainty of knowing the accuracy of the 3 hour timed interval between voids are clear disadvantages.
As an alternative to compensating for the time interval between voids, tests are available which work on random urine specimens. These tests require measurement of creatinine concentration in a specimen, however, and calculate the result in terms of the ratio of quantity of FSH to quantity of creatinine. In this case, a disadvantage is the requirement to measure the creatinine concentration as well as the FSH concentration.
Tests are available which measure urine FSH levels directly, but these suffer from technical difficulties in terms of ovarian reserve measurements. The tests are designed for indicating the onset of the menopause and give a yes/no indication based on a threshold value of 25 mIU/ml (standardised against the WHO Second International Standard IS 80/552) but it has been found by the present inventors that this threshold value is too high for measuring ovarian reserve.
It is an object of the present invention to provide assays which can distinguish between normal and diminished ovarian reserve based on urine samples. It is a further object to provide such tests which allow direct measurement from urine, which avoid complex calibration steps, and which are suited to home use. In particular, it is an object to provide tests which avoid pre-treatment of the specimen, the need for accurate timing, comparisons with standard creatinine concentrations, or volume measurement.